US6120788A - Bioabsorbable triglycolic acid poly(ester-amide)s - Google Patents

Bioabsorbable triglycolic acid poly(ester-amide)s Download PDF

Info

Publication number
US6120788A
US6120788A US09/174,136 US17413698A US6120788A US 6120788 A US6120788 A US 6120788A US 17413698 A US17413698 A US 17413698A US 6120788 A US6120788 A US 6120788A
Authority
US
United States
Prior art keywords
formula
ch
ester
amide
polymer
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
Application number
US09/174,136
Inventor
Thomas Harry Barrows
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Aderans Research Institute Inc
Original Assignee
BioAmide Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to US6206497P priority Critical
Application filed by BioAmide Inc filed Critical BioAmide Inc
Priority to US09/174,136 priority patent/US6120788A/en
Assigned to BIOAMIDE, INC. reassignment BIOAMIDE, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: BARROWS, THOMAS H.
Application granted granted Critical
Publication of US6120788A publication Critical patent/US6120788A/en
Assigned to ADERANS RESEARCH INSTITUTE, INC. reassignment ADERANS RESEARCH INSTITUTE, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: BIOAMIDE, INC.
Anticipated expiration legal-status Critical
Application status is Expired - Fee Related legal-status Critical

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08GMACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G69/00Macromolecular compounds obtained by reactions forming a carboxylic amide link in the main chain of the macromolecule
    • C08G69/44Polyester-amides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION, OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS, OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS, OR SURGICAL ARTICLES
    • A61L17/00Materials for surgical sutures or for ligaturing blood vessels ; Materials for prostheses or catheters
    • A61L17/06At least partially resorbable materials
    • A61L17/10At least partially resorbable materials containing macromolecular materials
    • A61L17/105Polyesters not covered by A61L17/12
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION, OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS, OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS, OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/18Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10TTECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T428/00Stock material or miscellaneous articles
    • Y10T428/29Coated or structually defined flake, particle, cell, strand, strand portion, rod, filament, macroscopic fiber or mass thereof
    • Y10T428/2913Rod, strand, filament or fiber
    • Y10T428/2973Particular cross section
    • Y10T428/2975Tubular or cellular

Abstract

This invention relates to fiber-forming bioabsorbable poly(ester-amide)s made by the polymerization of diamidediols with 3,6-dioxaoctanedioic acid, also known as "triglycolic acid". More specifically it relates to diol terminated poly(ester-amide)s of triglycolic acid that are optionally further reacted with glycolide, lactide, trimethylene carbonate, epsilon-caprolactone, or p-dioxanone, or mixtures of said cyclic monomers to produce the corresponding block copolymers. Said polymers are useful in the production of surgical sutures having superior performance characteristics including low bending stiffness and in the production of other fiber-based bioabsorbable implants and molded devices.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. Provisional Application Ser. No. 60/062,064, filed Oct. 16, 1997.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

Not applicable.

FIELD OF THE INVENTION

This invention relates to new and useful fiber-forming biabsorbable polymeric materials, such as bioabsorbable triglycolic acid poly(ester-amides)s, derived from reacting diamidediols with a diacid chloride deriviative of 3,6-dioxaoctanedioic acid, also known as "triglycolic acid". This invention also relates to new and useful diol terminated poly(ester-amide)s of triglycolic acid made by the polymerization of diamine diols with triglycolic acid poly(ester-amides)s, and to products of reacting such diol terminated poly(ester-amide)s with cyclic monomers to produce block copolymers. This invention further relates to methods of making new and useful fiberous bioabsorbable implants, including surgical sutures and molded devices, of such block copolymers or other polymeric materials.

BACKGROUND OF THE INVENTION

Since the first synthetic absorbable suture made from braided multifilaments of poly(glycolic acid) was introduced in about the year 1970, advancements in the design and synthesis of bioabsorbable polymers have resulted in continuous improvements in absorbable suture products.

In addition to the suture application, high strength, highly flexible, tough, and durable fibers that possess a prolonged flex fatigue life are needed for use as braided, knitted, woven, or non-woven implants to augment and temporarily reinforce autologous tissue grafts or to serve as scaffolds for tissue regeneration. One example of such an implant is known as a ligament augmentation device (LAD) used to reconstruct the anterior cruciate ligament (ACL) of the knee. Bioabsorbable fibers of the prior art, such as poly(L-lactic acid) (PLA), have not been successful in this application due to low flex fatigue life, shedding of wear debris due to the brittle nature of the fibers, and prolonged bioabsorption time.

Other well known uses for bioabsorbable polymers that have not been fully realized or perfected with available polymers of the prior art include scaffolds for tissue engineering, bioabsorbable knitted vascular grafts, drug-releasing devices, growth factor-releasing implants for bone and tissue regeneration, and fiber-reinforced composites for orthopedic applications. For example, composites of polymers reinforced with dissimilar materials, such as dissolvable glass fiber reinforced poly(lactic acid) are unacceptable for use as implants, the following reasons. Although dissolvable glass fibers provide high modulus needed for the composite to have high initial strength and stiffness, adhesion between glass and polymer invariably fails prematurely in vivo resulting in devices with unacceptable in vivo performance.

Self-reinforced composites were developed as an alternative to composites of polymers reinforced with dissimilar materials, such as those described above. In self-reinforced fiber composites both reinforcing fibers and matrix are made of the same material. Although the stiffness is lower than can be achieved with glass fibers, this alternative type of composite ensures good adhesion between fiber and matrix and thus offers the possibility of longer lasting in vivo strength. Self-reinforced poly(glycolic acid) (PGA) rods, pins and screws made by hot pressing or sintering PGA fibers have shown promise in clinical use. The main disadvantage of PGA in general is that it degrades too fast for orthopedic applications and releases an excessive concentration of acidic degradation products into the surrounding tissue.

Despite the advancements in the art of producing polymeric materials and methods for making polymeric materials suitable for use in sutures, molded devices, and similar surgical devices. Specifically, there continues to be a need for new fibers that are monofilament, have high initial tensile knot strength, retain useful strength in vivo for about two weeks or longer, are fully bioabsorbed within a few months after strength loss, and have very low bending stiffness.

BRIEF SUMMARY OF THE INVENTION

The present invention consists of a biabsorbable polymer of the general formula (I): ##STR1## wherein, x is from 2 to 10, m and n are independently from 0 to 2000, p is from 10 to 2000, and A is comprised of from 0 to 90 mole % A1 in combination with other structures selected from the group consisting of A2 and A3, wherein:

A1 is defined by the formula (II): --(CH2)y --, wherein y is from 2 to 10;

A2 is defined by the formula (III): ##STR2## wherein R1 is selected from the group consisting of: i) a linear alkene having from 1 to 5 carbon atoms;

ii) an ester defined by the formula(IV): --(CH2)x1 --O--(CH2)y1 --, wherein x1 (the end attached to the amide carbonyl) is from 1 to 4 and y1 (the end attached to the ester oxygen) is independently from 2 to 6; and

iii) a benzyl alkane of the formula(V): --(CH2)x2 --C6 H4 -- wherein the --(CH2)x2 end of the benzyl alkane is covalently attached to the amide carbonyl of formula III, and x2 is from 0 to 1; and

iv) an alkyl benzyl ester of the formula(VI): --(CH2)x3 --C6 H4 --O--(CH2)y3 --, wherein the --(CH2)x3 end of the alkyl benzyl ester is attached to the amide carbonyl of formula III, x3 is from 0 to 1, the (CH2)y3 -- end of the alkyl benzyl ester is attached to the ester oxygen of formula I, and y3 is independently from 2 to 6; and

R2 is selected from the group consisting of linear alkylenes having from 2 to 10 carbon atoms; and

A3 is defined by the following structure: ##STR3## wherein R3 is a divalent aliphatic or aromatic hydrocarbon radical having from 3 to about 8 carbon atoms; and

E2 is defined by a formula selected from the group of formulae consisting of:

formula (V): [--CO--CHR4 --O--], wherein R4 is selected from the group consisting of --H (from glycolide) and --CH3 (from lactide);

formula (VI): [--CO--O--(CH2)3 --O--];

formula (VII): [--CO--CH2 --O--(CH2)2 --O--];

formula (VIII): [--CO--(CH2)5 --O--]; and

combinations of formula V to VIII; and

E1 has the same structure as E2 except that the orientation of the formula of E1 is reversed.

In an alternative embodiment, the invention is the bioabsorbable polymer of general formula (I), above, wherein x is 2, and except as indicated all the other variables in the formula are defined as described above, except that:

A2 is defined by formula (III): ##STR4## wherein: R1 is selected from the group consisting of: i) a linear alkene having from 1 to 5 carbon atoms;

ii) an ester defined by formula(IV): --(CH2)x1 --O--(CH2)y1 --, wherein the --(CH2)x1, end of the ester is attached to the amide carbonyl of formula (III), x1 is from 1 to 4 and y1 is independently from 2 to 6;

iii) a benzyl alkane of formula(V): ##STR5## wherein the --(CH2)x2 end of the benzyl alkane is covalently attached to the amide carbonyl of formula III, and x2 is from 0 to 1; and

iv) an alkyl benzyl ether of formula(VI): ##STR6## wherein the --(CH2)x3 end of the alkyl benzyl ester is attached to the amide carbonyl of formula III, x3 is from 0 to 1, the (CH2)y3 -- end of the alkyl benzyl ester is attached to the ester oxygen of formula I, and y3 is independently from 2 to 6; and

R2 is selected from the group consisting of linear alkyenes having from 4 to 10 carbon atoms.

The present invention also consists of bioabsorbable materials made from the bioabsorbable polymer of the invention designed for in vivo use or implantation, including but not limited to bioabsorbable sutures, and a self-reinforced device comprised of fused or sintered fibers of the bioabsorbable polymer. The present invention further consists of a method of making self-reinforced materials from the bioabsorbable polymer of this invention.

DETAILED DESCRIPTION OF THE INVENTION

The diacid chloride derivative of 3,6-dioxaoctanedioic acid, commonly known as "triglycolyl chloride", has been discovered in the present invention to be an ideal monomer or comonomer for polymerization with diamidediols to produce poly(ester-amide)s capable of forming flexible, tenacious monofilament fibers with adequate bioabsorption time for use as surgical suture. Triglycolic acid is inexpensive and readily available since it can be economically produced by nitric acid oxidation of triethylene glycol. The conversion of triglycolic acid into triglycolyl chloride is described in U.S. Pat. No. 3,966,766, the teachings of which are incorporated herein (see Example 1, "Preparation of triglycolyl chloride").

Since polymers formed by polymerization of diamidediols with triglycolyl chloride are expected to have low softening points, it may not be feasible to use the suspension polymerization method described in U.S. Pat. No. 5,286,837, the teachings of which are incorporated herein. This method fails to yield high molecular weight product if the diamidediol suspension "melts down" due to low oligomer melting point. In this case an alternative method of forming poly(ester-amide)s from diacid chlorides and diamidediols in solution can be utilized (see S. Katayama et al., Journal of Applied Polymer Science, 20, 975-994 (1976), incorporated herein by reference).

An alternative method of forming triglycolic acid poly(ester-amide)s that may be preferable to the use of triglycolyl chloride is to melt polyesterify the diamidediol by reacting it with the dimethyl ester or diethyl ester of triglycolic acid with an appropriate catalyst and with distillation of methanol or ethanol, respectively, as the condensation reaction byproduct. If a slight excess of diamidediol is used, the final reaction conditions of high temperature and low pressure will remove traces of alcohol and any unreacted dimethyl or diethyl triglycolate to give a diol terminated poly(ester-amide). Another method for producing diol terminated poly(ester-amide)s with improved molecular weight is described in U.S. Pat. Nos. 4,209,607 and 4,226,243, the teachings of which are incorporated herein. In this procedure an excess of an aliphatic diol having greater volatility than the diamidediol is added with an appropriate catalyst to an equamolar mixture of diamidediol and diacid diester. As the mixture is heated under conditions of increasing temperature and decreasing pressure, excess aliphatic diol is distilled from the mixture along with the condensation reaction byproduct alcohol to give exceptionally high molecular weight poly(ester-amide) that is diol terminated.

Since it is known that molten glycolide and molten lactide are solvents for poly(ester-amide)s (see U.S. Pat. No. 5,502,092, the teachings of which are incorporated herein), glycolide, lactide, or other cyclic monomers or mixtures of cyclic monomers and the appropriate catalyst (e.g. stannous octoate) can be added to the molten polymer to initiate the polymerization of polyglycolide or polylactide or other polymeric end blocks on the diol terminated poly(ester-amide). This process serves both to increase the polymer molecular weight and to introduce highly crystalline "hard segments" (in the case of glycolide or L-lactide) into the low Tg, soft, rubbery, yet strong and tough, ether containing poly(ester-amide). This type of polymer can be readily freed of unreacted glycolide or lactide, purified, and extruded into monofilament suture by well known methods. Procedures applicable to the synthesis of polyglycolide block copolymers of the present invention are described in U.S. Pat. Nos. 4,429,080; 5,133,739; 5,403,347; and 5,522,841, the teachings of which are incorporated herein.

1,6-Di(hydroxyacetamido)hexane, is a preferred diamidediol because it has been reported to have passed various safety and toxicity tests, is water soluble, yet does not contribute to premature fiber strength loss known to occur with shorter chain diamidediols such as 1,2-di(hydroxyacetamido)ethane.

Bioabsorption of poly(ester-amide)s of the present invention occurs at a reliable rate and is not limited by the choice of the diamidediol since the glycolate ester-like nature of the triglycolate moiety has been discovered in the present invention to be the primary structural feature controlling the rate of polymer hydrolysis. Thus diamidediols formed from ether containing hydroxy acids such as hydroxyethoxy acetic acid, hydroxytetramethyleneoxyacetic acid, and hydroxyhexamethyleneoxyacetic acid can be used to obtain diamidediols that have adequate water solubility and contain ether linkages for improved polymer flexibility. Alternatively, diamidediols also can be formed from hydroxyacids longer than glycolic acid that do not contain ether linkages. An example is 1,6-di(6-hydroxycaproamido)hexane formed by the reaction of 2 moles of caprolactone with 1 mole of hexamethylenediamine (see U.S. Pat. No. 3,025,323, the teachings of which are incorporated herein).

The preparation of hydroxyethoxyacetic acid as a precursor for p-dioxanone used in the synthesis of poly(dioxanone) has been described in U.S. Pat. No. 4,052,988, the teachings of which are incorporated herein. In this procedure sodium metal is reacted with an excess of ethylene glycol and then chloroacetic acid is added in an amount calculated to be one half the molar quantity of the sodium used. This gives the sodium salt of hydroxyethoxyacetic acid which can be converted into the free acid by precipitation of sodium chloride with HCl. At this point a diamine can be added to produce a "nylon salt" precursor of the desired diamidediol which can then be isolated and converted into the diamidediol by heating with distillation of water as described in U.S. Pat. No. 4,529,792, the teachings of which are incorporated herein. In a similar fashion other hydroxyalkyleneoxyacetic acid diamidediols can be obtained with the use of longer chain glycols such as tetramethylene glycol and hexamethylene glycol. In addition, chloroacids with longer methylene chain lengths also can be used in the reaction with glycols to give ether-containing hydroxy acids. For example, 3-chloropropionic acid, 4-chlorobutyric acid, and 5-chlorovaleric acid all can be used in place of chloroacetic acid to produce ether-containing hydroxy acids that are useful in the present invention.

Alternatively, if a stiff bioabsorbable polymer is desired for non-suture applications such as orthopedic fixation pins and rods, a rigid amidediol can be created for example by the reaction of one mole of a diamine with 2 moles of an aromatic hydroxyacid such as 4-hydroxybenzoic acid, 4-hydroxyphenylacetic acid, 4-hydroxyethoxybenzoic acid, 4-(hydroxyethoxy)phenylacetic acid, and the like. A distinct advantage of the present invention is that the chemical structure of the diamidediol is not limited to those structures that contribute to hydrolytic degradability of the polymer since hydrolytic degradablility is assured by the presence of triglycolic acid ester linkages. Methods of processing polymers of the present invention into useful forms include melt spinning of fibers, injection molding of parts, and hot pressing or sintering together bundles of fibers or plies of braided, woven, or non-woven fiber layers into self-reinforced composites. Fibers can also be processed into useful structural supports for example as bone fragment fixation devices and inter vertebral discs for spinal fusion by solvent welding. Thus a solution of the polymer can be made in a solvent that does not attack the crystalline regions of the fiber at room temperature. This solution can then be used to glue the fibers together. After evaporation of the solvent by vacuum drying, the composite can be further consolidated and strengthened by hot pressing at a temperature below the crystalline melting temperature of the fiber. This approach also allows for the uniform introduction of drugs or growth factors into the composite by suspending or dissolving the drug or growth factor into the polymer solution used for solvent welding.

An example of a bioabsorbable device made by this technique is a porous, fiber self-reinforced, bone growth factor-releasing implant for accelerated spinal fusion. Such devices are needed to eliminate the pain, morbidity, and expense associated with the use of autologous bone grafts to achieve spinal fusion.

Other methods of processing and utilizing polymers of the present invention will be apparent to those skilled in the art of polymer processing and surgical device fabrication.

DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

The polymers of the present invention have a plurality of units of the general formula:

H--[--E--].sub.m --O--A--[--O--CO--CH.sub.2 --O--(CH.sub.2).sub.x --O--CH.sub.2 --CO--O--A--].sub.p --O--[--E--].sub.n --H

wherein x is from 2 to 10, m and n are independently from 0 to 2000, p is from 10 to 2000, and A is comprised of from 0 to 90 mole % B in combination with other structures selected from the group consisting of C and D wherein:

B is defined by the following structure:

--(CH.sub.2).sub.x --

wherein x is from 2 to 10; and

C is defined by the following structure:

--R1--CO--NH--R2--NH--CO--R1--

wherein:

a) R1 is selected from the group consisting of:

i) linear alkylenes having from 1 to 5 carbon atoms; and

ii) --(CH2)x --O--(CH2)y -- wherein x (the end attached to the amide carbonyl) is from 1 to 4 and y (the end attached to the ester oxygen) is independently from 2 to 6; and

iii) --(CH2)x --C6 H4 -- wherein x (the end attached to the amide carbonyl) is from 0 to 1; and

iv) --(CH2)x --C6 H4 --O--(CH2)y -- wherein x (the end attached to the amide carbonyl) is from 0 to 1 and y (the end attached to the ester oxygen) is independently from 2 to 6; and

b) R2 is selected from the group consisting of linear alkylenes having from 2 to 10 carbon atoms; and

D is defined by the following structure:

--R3--NH--CO--CO--NH--R3--

wherein R3 is a divalent aliphatic or aromatic hydrocarbon radical having from 3 to about 8 carbon atoms; and

E is defined by the following structures:

I. [--CO--CHR4--O--] wherein R4 is selected from the group consisting of --H (from glycolide) and --CH3 (from lactide);

II. [--CO--O--(CH2)3 --O--]

III. [--CO--CH2 --O--(CH2)2 --O--]

IV. [--CO--(CH2)5 --O--]

and combinations thereof. Note that the above structures I. through IV. are drawn to represent replacement of E on the right side of the general formula and will be reversed for replacement of E on the left side of the general formula.

The preferred embodiments of the present invention are polymers with end blocks (E) of polyglycolide or polylactide wherein R1 is formed from glycolic acid or hydroxycaproic acid (e.g. via caprolactone), and R2 is --(CH2)6 --. These polymers have the advantages of excellent initial fiber strength retention in vivo due to resistance of moisture uptake, complete bioabsorption due to amidediol water solubility and the proven bioabsorbability of commercially available glycolic and lactic acid ester containing polymers.

EXAMPLES

The following Examples are illustrative of the invention described above. Actual synthetic preparation of these and other example polymers may be performed according to the general instructions set forth below.

Example 1 Poly[2,5-dioxahexane-1,6-di(carbonyloxy)hexane-1,6-di(amidocarbonylmethylene)]

Triglycolyl chloride is prepared according the procedure in U.S. Pat. No. 3,966,766, Example 1. 1,6-Di(hydroxyacetamido)hexane is prepared according to the method described in Example 1 of U.S. Pat. No. 4,343,931, the teachings of which are incorporated herein. These two monomers are then polymerized according to the solution polymerization method described in the literature (see S. Katayama, T. Murakami, Y. Takahashi, H. Serita, Y. Obuchi, and T. Ito, "Synthesis of alternating polyamide esters by melt and solution polycondensations of N,N'-di(6-hydroxycaproyl)diamines and N-6-hydroxycaproyl aminoalcohol with terephthalic and adipic methyl esters and dichlorides", Journal of Applied Polymer Science, 20, 975-994 (1976)).

Example 2 1,6-Hexanediol terminated poly[2,5-dioxahexane-1,6-di(carbonyloxy)hexane-1,6-di(amidocarbonylmethylene)]

Triglycolic acid diethyl ester is prepared from purified 3,6-dioxaoctanedioic acid (e.g. recrystallized from ethyl acetate) by reaction with excess ethanol. An example of an acceptable method of forming the diethyl ester is refluxing the triglycolic acid in ethanol with sulfuric acid as a catalyst with the use of 3A molecular sieves for removal of water in a Soxhlet extractor (see Fieser & Fieser, "Reagents for Organic Synthesis", page 705, John Wiley and Sons, Inc., 1967). Vacuum distillation of the diethyl ester will yield a pure, colorless liquid suitable for polymerization. High purity (e.g. triple recrystallized) 1,6-di(hydroxyacetamido)hexane and an equamolar amount of redistilled diethyl triglycolate are reacted together with a 20% molar excess of 1,6-hexanediol and a catalytic amount of a titanate catalyst such as Tyzor TOT™ (E.I. du Pont de Nemours & Co., Wilminton, Del. 19898) as described in the procedure of U.S. Pat. No. 4,226,243 Example 6 (B & C), optimum conditions of time, temperature, and pressure to be determined. Distillation of excess 1,6-hexanediol yields a high molecular weight diol-terminate poly(ester-amide) suitable for extrusion into high strength, flexible, and fully bioabsorbable surgical suture.

Example 3 Block copolymer of polyglycolide with poly[2,5-dioxahexane-1,6-di(carbonyloxy)hexane-1,6-di(amidocarbonylmethylene)]

Example 2 is repeated except that after an acceptable molecular weight is obtained (e.g. inherent viscosity of about 0.6 to 0.9 in 2,2,2-trifluoroethanol at 0.5% concentration at 30° C.) and the last traces of alcohol, diol, and any unreacted diethyl triglycolate have been removed under high vacuum, the melted polymer is cooled to about 130° C. and about one part by weight of glycolide for each about 4 parts by weight of the poly(ester-amide) is added to the reactor along with an appropriate amount of catalyst such as stannous octoate. The reaction is then heated up to about 195 ° C. and additional glycolide is added and block copolymerized with the poly(ester-amide) according to the general procedure for this type of reaction described in U.S. Pat. No. 5,522,841 Examples 1, 2, and 3. The resultant block copolymer can then be further processed as necessary to remove any unreacted glycolide and or homopolymer and melt extruded into monofilament suture. Such suture has the advantage of exceptionally high strength and flexibility.

Example 4 Poly[2,5-dioxahexane-1,6-di(carbonyloxy))hexane-1,6-di(amidocarbonylmethyleneoxyethylene)]

The preparation of hydroxyethoxyacetic acid has been described in U.S. Pat. No. 4,052,988, the teachings of which are incorporated herein. In this procedure sodium metal is reacted with an excess of ethylene glycol and then chloroacetic acid is added in an amount calculated to be one half the molar quantity of the sodium used. This gives the sodium salt of hydroxyethoxyacetic acid which can be converted into the free acid by precipitation of sodium chloride with HCl. At this point hexamethylenediamine is added to produce a "nylon salt" precursor of the desired diamidediol which is then isolated and converted into the desired diamidediol by heating with distillation of water as described in U.S. Pat. No. 4,529,792, the teachings of which are incorporated herein. 1,6-Di(hydroxyethoxyacetamido)hexane alternatively can be prepared by heating 2 moles of ρ-dioxanone with one mole of hexamethylenediamine. The product is purified by recrystallization and vacuum dried. This diamidediol monomer is then polymerized with triglycolyl chloride as in Example 1.

Example 5 Poly[2,5-dioxahexane-1,6-di(carbonyloxy)butane-1,4-di(amidocarbonyl-1,4-phenylene)]

1,4-Di(4-hydroxybenzamido)butane is prepared by heating 2 moles of 4-hydroxybenzoic acid with one mole of butanediamine with distillation of water. The product is purified by recrystallization, vacuum dried, and ground to a fine powder. This diamidediol monomer is then polymerized with triglycolyl chloride as in Example 1.

Example 6 Poly[2,5-dioxahexane-1,6-di(carbonyloxy)decane-1,10-di(amidocarbonylmethylene-1,4-phenylene)]

1,4-Di(4-hydroxyphenylacetamido)decane is prepared by heating 2 moles of 4-hydroxyphenylacetic acid with one mole of decanediamine with distillation of water. The product is purified by recrystallization, vacuum dried, ground to a fine powder, and polymerized with triglycolyl chloride as in Example 1.

Example 7 Poly[2,5-dioxahexane-1,6-di(carbonyloxy)hexane-1,6-di(amidocarbonylmethyleneoxyhexamethylene)]

Hydroxyhexamethyleneoxyacetic acid is prepared in a manner similar to the preparation of hydroxyethoxyacetic acid described in Example 4 except that 1-6-hexanediol is used in place of ethylene glycol in the reaction in which sodium is reacted with the glycol followed by the addition of chloroacetic acid. Di(hydroxyhexamethyleneoxyacetamido)hexane is prepared by heating 2 moles of hydroxyhexamethyleneoxyacetic acid with one mole of hexamethylenediamine with distillation of water. The product is purified by recrystallization and vacuum dried. This diamidediol monomer is then polymerized with triglycolyl chloride as in Illustraton 1.

Example 8 Poly[2,5-dioxahexane-1,6-di(carbonyloxy)hexane-1,6-di(amidocarbonylpentamethylene)]

1,6-Di(6-hydroxycaproamido)hexane prepared according the procedure in U.S. Pat. No. 3,025,323 is polymerized with triglycolyl chloride as in Example 1.

Example 9 Poly[2,5-dioxahexane-1,6-di(carbonyloxy)hexane-1,6-di(amidocarbonyltetramethyleneoxyethylene)]

Hydroxyethoxyvaleric acid is prepared by in a manner similar to the preparation of hydroxyethoxyacetic acid except that 5-chlorovaleric acid is used in place of chloroacetic acid. 1,6-Di(hydroxyethoxyvaleramido)hexane is prepared by heating 2 moles of hydroxyethoxyvaleric acid with one mole of hexamethylenediamine with distillation of water. The product is purified by recrystallization and vacuum dried. This diamidediol monomer is then polymerized with triglycolyl chloride as in Example 1.

Example 10 Poly[2,5-dioxahexane-1,6-di(carbonyloxy)hexane-1,6-di(amidocarbonyl-1,4-phenyleneoxyhexamethylene)]

4-Hydroxy(hexamethyleneoxy)benzoic acid is prepared in a manner similar to the preparation of hydroxyhexamethyleneoxyacetic acid except that 4-chlorobenzoic acid is used in place of chloroacetic acid. This diamidediol monomer is then polymerized with triglycolyl chloride as in Example 1.

Examples 11-17

The polymers described in Examples 4-10 above, respectively, are prepared by the method described in Example 2 above to give the corresponding 1,6-hexanediol terminated polymers.

Example 18 1,6-Hexanediol terminated poly N,N'-bis(hexamethylene)oxamido triglycolate

N,N'-bis(6-hydroxyhexamethylene)oxamide prepared according to the procedure in U.S. Pat. No. 4,226,243 Example 3 is reacted with 1,6-hexanediol and diethyl triglycolate, as a substitute for diethyl oxalate, according to the procedure in U.S. Pat. No. 4,226,243 Example 6 parts B and C.

Examples 19-26

The polymers described in Examples 11-18 above, respectively, are further reacted with glycolide as described in Example 3 above to give the corresponding polyglycolide block copolymers.

Example 27 Block copolymer of polylactide with poly[2,5-dioxahexane-1,6-di(carbonyloxy)hexane-1,6-di(amidocarbonylmethylene)]

Example 3 is repeated with the substitution of L-lactide for glycolide.

Example 28 Block copolymer of epsilon-caprolactone with poly[2,5-dioxahexane-1,6-di(carbonyloxy)hexane-1,6-di(amidocarbonylpentamethylene)]

The polymer of Example 15, i.e. 1,6-hexanediol terminated poly[2,5-dioxahexane-1,6-di(carbonyloxy)hexane-1,6-di(amidocarbonylpentamethylene)] is further polymerized with epsilon-caprolactone according to the procedure in Example 3 with the substitution of epsilon-caprolactone for glycolide.

Example 29 Block copolymer of ρ-dioxanone and trimethylene carbonate with poly[2,5-dioxahexane-1,6-di(carbonyloxy)hexane-1,6-di(amidocarbonylmethylene)]

Example 3 is repeated with the substitution of a mixture of trimethylene carbonate and ρ-dioxanone for glycolide.

Example 30 1,6-Hexanediol terminated poly[2,13-dioxatetradecane-1,14-di(carbonyloxy)ethane-1,2-di(amidocarbonylmethylene)]

Example 2 is repeated with the substitution of 3,14-dioxahexadecanedioic acid for 3,6-dioxaoctanedioic acid and the substitution of 1,2-di(hydroxyacetamido)ethane for 1,6-di(hydroxyacetamido)hexane.

Example 31 Growth factor-releasing bioabsorbable fiber-reinforced implant for bone regeneration

The polymer of Example 27 is extruded into multifilament yarn and hot drawn to produce high tenacity fiber via the development of molecular orientation and strain-induce crystallization. The yarn is then cut into short staple fibers of about 2 to 15 mm length and formed into an air-laid or wet-laid web by standard nonwoven fiber processing techniques. A solution of the same polymer is prepared by heating and dissolving the polymer in anhydrous N-methyl-2-pyrollidinone and cooling to room temperature. Finely divided recombinant human bone morphogenic protein is homogeneously dispersed in this solution and the mixture is then impregnated into the above fabric. The soaked fabric is then subjected to low temperature vacuum drying such that the solvent is slowly and completely evaporated. These conditions are optimized such that the solvent mixture does not dissolve or weaken the fibers in the fabric but instead causes the fibers to become bonded into a highly porous, three-dimensionally stable tissue regeneration matrix. The fabric is cut into appropriate sizes and then packaged and sterilized by ethylene oxide.

This material when implanted as a space-filling device in a bone defect induces new bone formation under the influence of the slowly released bone growth factor. The strength of the fiber-reinforced structure meanwhile maintains an appropriate matrix porosity during the bone formation process. Ultimately the implant is completely bioabsorbed and replaced with normal remodeled bone.

While the present invention has now been described and exemplified with some specificity, those skilled in the art will appreciate the various modifications, including variations, additions, and omissions, that may be made in what has been described. Accordingly, it is intended that these modifications also be encompassed by the present invention and that the scope of the present invention be limited solely by the broadest interpretation that lawfully can be accorded the appended claims.

Claims (13)

What is claimed is:
1. A bioabsorbable polymer comprising a poly(ester-amide) of the general formula (I): ##STR7## wherein, x is from 2 to 10, m and n are independently from 0 to 2000, p is from 10 to 2000, and A is comprised of from 0 to 90 mole %
A1 in combination with other structures selected from the group consisting of A2 and A3, wherein:
A1 is defined by formula (II): --(CH2)y --, wherein y is from 2 to 10;
A2 is defined by formula (III): ##STR8## wherein: R1 is selected from the group consisting of:
i) a linear alkene having from 1 to 5 carbon atoms;
ii) an ester defined by formula(IV): --(CH2)x1 --O--(CH2)y1 --, wherein the --(CH2)x1 end of the ester is attached to the amide carbonyl of formula (III), x1 is from 1 to 4 and y1 is independently from 2 to 6;
iii) a benzyl alkane of formula(V): --(CH2)x2 --C6 H4 -- wherein the --(CH2)x2 end of the benzyl alkane is covalently attached to the amide carbonyl of formula III, and x2 is from 0 to 1; and
iv) an alkyl benzyl ether of formula(VI): --(CH2)x3 --C6 H4 --O--(CH2)y3 --, wherein the --(CH2)x3 end of the alkyl benzyl ester is attached to the amide carbonyl of formula III, x3 is from 0 to 1, the (CH2)y3 -- end of the alkyl benzyl ester is attached to the ester oxygen of formula I, and y3 is independently from 2 to 6; and
R2 is selected from the group consisting of linear alkylenes having from 2 to 10 carbon atoms; and
A3 is defined by formula (VI): ##STR9## wherein R3 is a divalent aliphatic or aromatic hydrocarbon radical having from 3 to about 8 carbon atoms; and
E2 is defined by a formula selected from the group of formulae consisting of:
formula (VII): [--CO--CHR4 --O--], wherein R4 is selected from the group consisting of --H (from glycolide) and --CH3 (from lactide);
formula (VIII): [--CO--O--(CH2)3 --O--];
formula (IX): [--CO--CH2 --O--(CH2)2 --O--];
formula (X): [--CO--(CH2)5 --O--]; and
combinations of formula VII to X; and
E1 has the same structure as E2 except that the orientation of the formula of E1 is reversed.
2. The polymer of claim 1, wherein n and m have an average value between about 50 and about 1000, and p has an average value between about 20 and about 1000.
3. The polymer of claim 1 wherein A1 is formed from 1,6-hexanediol.
4. The polymer of claim 1 wherein A is formed from 1,6-di(hydroxyacetamido)hexane.
5. The polymer of claim 1 wherein A is formed from N,N'-bis(6-hydroxyhexamethylene)oxamide.
6. The polymer of claim 1 wherein A is formed from 1,6-di(6-hydroxycaproamido)hexane.
7. The polymer of claim 1 characterized in that the poly(ester-amide) of formula (I) is prepared by:
a) reacting a linear aliphatic diamine of 2 to 10 methylene carbon atoms with a lactone or a hydroxyacid selected from the following formulae: ##STR10## wherein x is from 2 to 5; formula (a-II): HO--R1 --COOH
wherein R1 is selected from the group consisting of:
i) linear alkylenes having from 1 to 5 carbon atoms; and
ii) --(CH2)x --O--(CH2)y -- wherein x (the end attached to the carbonyl) is from 1 to 4 and y (the end attached to the oxygen) is independently from 2 to 6;
iii) --(CH2)x --C6 H4 -- wherein x (the end attached to the carbonyl) is from 0 to 1; and
iv) --(CH2)x --C6 H4 --O--(CH2)y -- wherein x (the end attached to the carbonyl) is from 0 to 1 and y (the end attached to the oxygen) is independently from 2 to 6 to produce a diamidediol; and
b) melt polyesterifying the diamediol by reacting said diamidediol with 3,6-dioxaoctanedioic acid, its diacid chloride, dimethyl ester, or diethyl ester derivatives to produce the poly(ester-amide).
8. The polymer of claim 1 characterized in that the poly(ester-amide) of formula (I) is prepared by:
a) providing a diamidediol of the following structure:
HO--R--NH--CO--CO--NH--R--OH , wherein R is a divalent aliphatic or aromatic hydrocarbon radical having from 3 to about 8 carbon atoms; and
b) melt polyesterifying the diamediol by reacting said diamidediol with 3,6-dioxaoctanedioic acid, its diacid chloride, dimethyl ester, or diethyl ester derivatives to produce the poly(ester-amide).
9. A bioabsorbable surgical suture made from a polymer of claim 1.
10. A bioabsorbable polymer comprising a poly(ester-amide) of the general formula (XV): ##STR11## wherein, m and n are independently from 0 to 2000, p is from 10 to 2000, and A is comprised of from 0 to 90 mole %
A1 in combination with other structures selected from the group consisting of A2 and A3, wherein:
A1 is defined by formula (II): --(CH2)y --, wherein y is from 2 to 10;
A2 is defined by formula (III): ##STR12## wherein: R1 is selected from the group consisting of: i) a linear alkene having from 1 to 5 carbon atoms;
ii) an ester defined by formula(IV): --(CH2)x1 --O--(CH2)y1 --, wherein the --(CH2)x1 end of the ester is attached to the amide carbonyl of formula (III), x1 is from 1 to 4 and y1 is independently from 2 to 6;
iii) a benzyl alkane of formula(V): ##STR13## wherein the --(CH2)x2 end of the benzyl alkane is covalently attached to the amide carbonyl of formula III, and x2 is from 0 to 1; and
iv) an alkyl benzyl ether of formula(VI): ##STR14## wherein the --(CH2)x3 end of the alkyl benzyl ester is attached to the amide carbonyl of formula III, x3 is from 0 to 1, the (CH2)y3 -- end of the alkyl benzyl ester is attached to the ester oxygen of formula I, and y3 is independently from 2 to 6; and
R2 is selected from the group consisting of linear alkylenes having from 2 to 10 carbon atoms; and
A3 is defined by formula (VI): ##STR15## wherein R3 is a divalent aliphatic or aromatic hydrocarbon radical having from 3 to about 8 carbon atoms; and
E2 is defined by a formula selected from the group of formulae consisting of:
formula (VII): [--CO--CHR4 --O--], wherein R4 is selected from the group consisting of --H (from glycolide) and --CH3 (from lactide);
formula (VIII): [--CO--O--(CH2)3 --O--];
formula (IX): [--CO--CH2 --O--(CH2)2 --O--];
formula (X): [--CO--(CH2)5 --O--]; and
combinations of formula VII to X; and
E1 has the same structure as E2 except that the orientation of the formula of E1 is reversed.
11. The polymer of claim 10 characterized in that the poly(ester-amide) of formula (XV) is prepared by:
a) reacting a linear aliphatic diamine of 2 to 10 methylene carbon atoms with a lactone or a hydroxyacid selected from the following formulae: ##STR16## wherein x is from 2 to 5; formula (a-II): HO--R1 --COOH
wherein R1 is selected from the group consisting of:
i) linear alkylenes having from 1 to 5 carbon atoms;
ii) --(CH2)x1 --O--(CH2)y1 --, wherein the --(CH2)x1 end is attached to the carbonyl of formula (a-II), x1 is from 1 to 4 and y1 is independently from 2 to 6; ##STR17## wherein the --(CH2)x2 end is attached to the carbonyl of formula (a-II), x2 is from 0 to 1; and ##STR18## wherein the --(CH2)x3 end is attached to the carbonyl of formula (a-II), x3 is from 0 to 1, and y is independently from 2 to 6; to produce a diamidediol; and
b) melt polyesterifying the diamediol by reacting the diamidediol with a reagent selected from the group consisting of: 3,6-dioxaoctanedioic acid, its diacid chloride, dimethyl ester, and diethyl ester derivatives to produce a poly(ester-amide) polymer of formula(I).
12. The polymer of claim 7, wherein the polymer is a block copolymer prepared by further reacting said poly(ester-amide) with glycolide, lactide, trimethylene carbonate, ρ-dioxanone, or epsilon-caprolactone or combinations thereof to produce a block copolymer.
13. The polymer of claim 11, wherein the polymer is a block copolymer prepared by further reacting said poly(ester-amide) with glycolide, lactide, trimethylene carbonate, ρ-dioxanone, or epsilon-caprolactone or combinations thereof.
US09/174,136 1997-10-16 1998-10-16 Bioabsorbable triglycolic acid poly(ester-amide)s Expired - Fee Related US6120788A (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US6206497P true 1997-10-16 1997-10-16
US09/174,136 US6120788A (en) 1997-10-16 1998-10-16 Bioabsorbable triglycolic acid poly(ester-amide)s

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US09/174,136 US6120788A (en) 1997-10-16 1998-10-16 Bioabsorbable triglycolic acid poly(ester-amide)s
US09/630,118 US6365172B1 (en) 1997-10-16 2000-08-01 Device of bioabsorbable triglycolic acid poly(ester-amide)s, and methods of making the same

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US09/630,118 Division US6365172B1 (en) 1997-10-16 2000-08-01 Device of bioabsorbable triglycolic acid poly(ester-amide)s, and methods of making the same

Publications (1)

Publication Number Publication Date
US6120788A true US6120788A (en) 2000-09-19

Family

ID=26741822

Family Applications (2)

Application Number Title Priority Date Filing Date
US09/174,136 Expired - Fee Related US6120788A (en) 1997-10-16 1998-10-16 Bioabsorbable triglycolic acid poly(ester-amide)s
US09/630,118 Expired - Fee Related US6365172B1 (en) 1997-10-16 2000-08-01 Device of bioabsorbable triglycolic acid poly(ester-amide)s, and methods of making the same

Family Applications After (1)

Application Number Title Priority Date Filing Date
US09/630,118 Expired - Fee Related US6365172B1 (en) 1997-10-16 2000-08-01 Device of bioabsorbable triglycolic acid poly(ester-amide)s, and methods of making the same

Country Status (1)

Country Link
US (2) US6120788A (en)

Cited By (89)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6365172B1 (en) * 1997-10-16 2002-04-02 Bioamide, Inc. Device of bioabsorbable triglycolic acid poly(ester-amide)s, and methods of making the same
US20040054410A1 (en) * 2000-08-08 2004-03-18 Barrows Thomas H Scaffolds for tissue engineered hair
US20040068284A1 (en) * 2002-01-29 2004-04-08 Barrows Thomas H. Method for stimulating hair growth and kit for carrying out said method
US20050100609A1 (en) * 2001-03-30 2005-05-12 Claude Charles D. Phase-separated polymer coatings
US20050191748A1 (en) * 1999-02-08 2005-09-01 Aderans Research Institute, Inc. Filamentary means for introducing agents into tissue of a living host
US20050214344A1 (en) * 2004-03-26 2005-09-29 Aderans Research Institute, Inc. Tissue engineered biomimetic hair follicle graft
US20060062770A1 (en) * 2004-08-13 2006-03-23 Aderans Research Institute, Inc. Organogenesis from dissociated cells
US20070122387A1 (en) * 2005-11-22 2007-05-31 Aderans Research Institute, Inc. Hair grafts derived from plucked hair
US20070148138A1 (en) * 2005-11-22 2007-06-28 Aderans Research Institute, Inc. Hair follicle graft from tissue engineered skin
US20080161489A1 (en) * 2006-12-28 2008-07-03 Adel Farhan Halasa Rubbery block polymers containing polylactone and rubber compounds including the same
US20080311044A1 (en) * 2007-06-12 2008-12-18 Aderans Research Institute, Inc. Methods of determining hair follicle inductive properties
US7648727B2 (en) 2004-08-26 2010-01-19 Advanced Cardiovascular Systems, Inc. Methods for manufacturing a coated stent-balloon assembly
US7648725B2 (en) 2002-12-12 2010-01-19 Advanced Cardiovascular Systems, Inc. Clamp mandrel fixture and a method of using the same to minimize coating defects
US7682669B1 (en) 2001-07-30 2010-03-23 Advanced Cardiovascular Systems, Inc. Methods for covalently immobilizing anti-thrombogenic material into a coating on a medical device
US7691401B2 (en) 2000-09-28 2010-04-06 Advanced Cardiovascular Systems, Inc. Poly(butylmethacrylate) and rapamycin coated stent
US7699889B2 (en) 2004-12-27 2010-04-20 Advanced Cardiovascular Systems, Inc. Poly(ester amide) block copolymers
US7713637B2 (en) 2006-03-03 2010-05-11 Advanced Cardiovascular Systems, Inc. Coating containing PEGylated hyaluronic acid and a PEGylated non-hyaluronic acid polymer
US7735449B1 (en) 2005-07-28 2010-06-15 Advanced Cardiovascular Systems, Inc. Stent fixture having rounded support structures and method for use thereof
US7749263B2 (en) 2004-10-29 2010-07-06 Abbott Cardiovascular Systems Inc. Poly(ester amide) filler blends for modulation of coating properties
US7758880B2 (en) 2002-12-11 2010-07-20 Advanced Cardiovascular Systems, Inc. Biocompatible polyacrylate compositions for medical applications
US7758881B2 (en) 2004-06-30 2010-07-20 Advanced Cardiovascular Systems, Inc. Anti-proliferative and anti-inflammatory agent combination for treatment of vascular disorders with an implantable medical device
US7766884B2 (en) 2004-08-31 2010-08-03 Advanced Cardiovascular Systems, Inc. Polymers of fluorinated monomers and hydrophilic monomers
US7772359B2 (en) 2003-12-19 2010-08-10 Advanced Cardiovascular Systems, Inc. Biobeneficial polyamide/polyethylene glycol polymers for use with drug eluting stents
US7775178B2 (en) 2006-05-26 2010-08-17 Advanced Cardiovascular Systems, Inc. Stent coating apparatus and method
US7776926B1 (en) 2002-12-11 2010-08-17 Advanced Cardiovascular Systems, Inc. Biocompatible coating for implantable medical devices
US7785512B1 (en) 2003-07-31 2010-08-31 Advanced Cardiovascular Systems, Inc. Method and system of controlled temperature mixing and molding of polymers with active agents for implantable medical devices
US7785647B2 (en) 2005-07-25 2010-08-31 Advanced Cardiovascular Systems, Inc. Methods of providing antioxidants to a drug containing product
US7794743B2 (en) 2002-06-21 2010-09-14 Advanced Cardiovascular Systems, Inc. Polycationic peptide coatings and methods of making the same
US7795467B1 (en) 2005-04-26 2010-09-14 Advanced Cardiovascular Systems, Inc. Bioabsorbable, biobeneficial polyurethanes for use in medical devices
US7803394B2 (en) 2002-06-21 2010-09-28 Advanced Cardiovascular Systems, Inc. Polycationic peptide hydrogel coatings for cardiovascular therapy
US7803406B2 (en) 2002-06-21 2010-09-28 Advanced Cardiovascular Systems, Inc. Polycationic peptide coatings and methods of coating implantable medical devices
US7807210B1 (en) 2000-10-31 2010-10-05 Advanced Cardiovascular Systems, Inc. Hemocompatible polymers on hydrophobic porous polymers
US7807211B2 (en) 1999-09-03 2010-10-05 Advanced Cardiovascular Systems, Inc. Thermal treatment of an implantable medical device
US7820732B2 (en) 2004-04-30 2010-10-26 Advanced Cardiovascular Systems, Inc. Methods for modulating thermal and mechanical properties of coatings on implantable devices
US7823533B2 (en) 2005-06-30 2010-11-02 Advanced Cardiovascular Systems, Inc. Stent fixture and method for reducing coating defects
US7867547B2 (en) 2005-12-19 2011-01-11 Advanced Cardiovascular Systems, Inc. Selectively coating luminal surfaces of stents
US7892592B1 (en) 2004-11-30 2011-02-22 Advanced Cardiovascular Systems, Inc. Coating abluminal surfaces of stents and other implantable medical devices
US7976891B1 (en) 2005-12-16 2011-07-12 Advanced Cardiovascular Systems, Inc. Abluminal stent coating apparatus and method of using focused acoustic energy
US7985440B2 (en) 2001-06-27 2011-07-26 Advanced Cardiovascular Systems, Inc. Method of using a mandrel to coat a stent
US7985441B1 (en) 2006-05-04 2011-07-26 Yiwen Tang Purification of polymers for coating applications
US8003156B2 (en) 2006-05-04 2011-08-23 Advanced Cardiovascular Systems, Inc. Rotatable support elements for stents
US8007775B2 (en) 2004-12-30 2011-08-30 Advanced Cardiovascular Systems, Inc. Polymers containing poly(hydroxyalkanoates) and agents for use with medical articles and methods of fabricating the same
US8007526B2 (en) 2005-12-01 2011-08-30 Bezwada Biomedical, Llc Difunctionalized aromatic compounds and polymers therefrom
US8017140B2 (en) 2004-06-29 2011-09-13 Advanced Cardiovascular System, Inc. Drug-delivery stent formulations for restenosis and vulnerable plaque
US8017237B2 (en) 2006-06-23 2011-09-13 Abbott Cardiovascular Systems, Inc. Nanoshells on polymers
US8021676B2 (en) 2005-07-08 2011-09-20 Advanced Cardiovascular Systems, Inc. Functionalized chemically inert polymers for coatings
US8029816B2 (en) 2006-06-09 2011-10-04 Abbott Cardiovascular Systems Inc. Medical device coated with a coating containing elastin pentapeptide VGVPG
US8048441B2 (en) 2007-06-25 2011-11-01 Abbott Cardiovascular Systems, Inc. Nanobead releasing medical devices
US8048448B2 (en) 2006-06-15 2011-11-01 Abbott Cardiovascular Systems Inc. Nanoshells for drug delivery
US8052912B2 (en) 2003-12-01 2011-11-08 Advanced Cardiovascular Systems, Inc. Temperature controlled crimping
US8062350B2 (en) 2006-06-14 2011-11-22 Abbott Cardiovascular Systems Inc. RGD peptide attached to bioabsorbable stents
US8067025B2 (en) 2006-02-17 2011-11-29 Advanced Cardiovascular Systems, Inc. Nitric oxide generating medical devices
US8067023B2 (en) 2002-06-21 2011-11-29 Advanced Cardiovascular Systems, Inc. Implantable medical devices incorporating plasma polymerized film layers and charged amino acids
US8110211B2 (en) 2004-09-22 2012-02-07 Advanced Cardiovascular Systems, Inc. Medicated coatings for implantable medical devices including polyacrylates
US8109904B1 (en) 2007-06-25 2012-02-07 Abbott Cardiovascular Systems Inc. Drug delivery medical devices
US8147769B1 (en) 2007-05-16 2012-04-03 Abbott Cardiovascular Systems Inc. Stent and delivery system with reduced chemical degradation
US8173199B2 (en) 2002-03-27 2012-05-08 Advanced Cardiovascular Systems, Inc. 40-O-(2-hydroxy)ethyl-rapamycin coated stent
US8192752B2 (en) 2003-11-21 2012-06-05 Advanced Cardiovascular Systems, Inc. Coatings for implantable devices including biologically erodable polyesters and methods for fabricating the same
US8197879B2 (en) 2003-09-30 2012-06-12 Advanced Cardiovascular Systems, Inc. Method for selectively coating surfaces of a stent
US8293890B2 (en) 2004-04-30 2012-10-23 Advanced Cardiovascular Systems, Inc. Hyaluronic acid based copolymers
US8303651B1 (en) 2001-09-07 2012-11-06 Advanced Cardiovascular Systems, Inc. Polymeric coating for reducing the rate of release of a therapeutic substance from a stent
US8304012B2 (en) 2006-05-04 2012-11-06 Advanced Cardiovascular Systems, Inc. Method for drying a stent
US8309132B2 (en) 2008-05-16 2012-11-13 Bezwada Biomedical, Llc Bioabsorbable polyesteramides and uses thereof
US8357391B2 (en) 2004-07-30 2013-01-22 Advanced Cardiovascular Systems, Inc. Coatings for implantable devices comprising poly (hydroxy-alkanoates) and diacid linkages
US8435550B2 (en) 2002-12-16 2013-05-07 Abbot Cardiovascular Systems Inc. Anti-proliferative and anti-inflammatory agent combination for treatment of vascular disorders with an implantable medical device
US8506617B1 (en) 2002-06-21 2013-08-13 Advanced Cardiovascular Systems, Inc. Micronized peptide coated stent
US8568764B2 (en) 2006-05-31 2013-10-29 Advanced Cardiovascular Systems, Inc. Methods of forming coating layers for medical devices utilizing flash vaporization
US8586069B2 (en) 2002-12-16 2013-11-19 Abbott Cardiovascular Systems Inc. Anti-proliferative and anti-inflammatory agent combination for treatment of vascular disorders
US8597673B2 (en) 2006-12-13 2013-12-03 Advanced Cardiovascular Systems, Inc. Coating of fast absorption or dissolution
US8603634B2 (en) 2004-10-27 2013-12-10 Abbott Cardiovascular Systems Inc. End-capped poly(ester amide) copolymers
US8603530B2 (en) 2006-06-14 2013-12-10 Abbott Cardiovascular Systems Inc. Nanoshell therapy
US8609123B2 (en) 2004-11-29 2013-12-17 Advanced Cardiovascular Systems, Inc. Derivatized poly(ester amide) as a biobeneficial coating
US8673334B2 (en) 2003-05-08 2014-03-18 Abbott Cardiovascular Systems Inc. Stent coatings comprising hydrophilic additives
US8685431B2 (en) 2004-03-16 2014-04-01 Advanced Cardiovascular Systems, Inc. Biologically absorbable coatings for implantable devices based on copolymers having ester bonds and methods for fabricating the same
US8703169B1 (en) 2006-08-15 2014-04-22 Abbott Cardiovascular Systems Inc. Implantable device having a coating comprising carrageenan and a biostable polymer
US8703167B2 (en) 2006-06-05 2014-04-22 Advanced Cardiovascular Systems, Inc. Coatings for implantable medical devices for controlled release of a hydrophilic drug and a hydrophobic drug
US8741378B1 (en) 2001-06-27 2014-06-03 Advanced Cardiovascular Systems, Inc. Methods of coating an implantable device
US8778014B1 (en) 2004-03-31 2014-07-15 Advanced Cardiovascular Systems, Inc. Coatings for preventing balloon damage to polymer coated stents
US8778375B2 (en) 2005-04-29 2014-07-15 Advanced Cardiovascular Systems, Inc. Amorphous poly(D,L-lactide) coating
US9028859B2 (en) 2006-07-07 2015-05-12 Advanced Cardiovascular Systems, Inc. Phase-separated block copolymer coatings for implantable medical devices
US9056155B1 (en) 2007-05-29 2015-06-16 Abbott Cardiovascular Systems Inc. Coatings having an elastic primer layer
US9114198B2 (en) 2003-11-19 2015-08-25 Advanced Cardiovascular Systems, Inc. Biologically beneficial coatings for implantable devices containing fluorinated polymers and methods for fabricating the same
USRE45744E1 (en) 2003-12-01 2015-10-13 Abbott Cardiovascular Systems Inc. Temperature controlled crimping
US9339592B2 (en) 2004-12-22 2016-05-17 Abbott Cardiovascular Systems Inc. Polymers of fluorinated monomers and hydrocarbon monomers
US9364498B2 (en) 2004-06-18 2016-06-14 Abbott Cardiovascular Systems Inc. Heparin prodrugs and drug delivery stents formed therefrom
US9561309B2 (en) 2004-05-27 2017-02-07 Advanced Cardiovascular Systems, Inc. Antifouling heparin coatings
US9561351B2 (en) 2006-05-31 2017-02-07 Advanced Cardiovascular Systems, Inc. Drug delivery spiral coil construct
US9580558B2 (en) 2004-07-30 2017-02-28 Abbott Cardiovascular Systems Inc. Polymers containing siloxane monomers
US10076591B2 (en) 2010-03-31 2018-09-18 Abbott Cardiovascular Systems Inc. Absorbable coating for implantable device

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1781264B1 (en) * 2004-08-04 2013-07-24 Evonik Corporation Methods for manufacturing delivery devices and devices thereof
US20060089485A1 (en) * 2004-10-27 2006-04-27 Desnoyer Jessica R End-capped poly(ester amide) copolymers
EP2102144A4 (en) 2006-09-13 2011-03-23 Univ Rutgers Active agents and their oligomers and polymers
CA2709712C (en) 2007-12-20 2016-05-10 Surmodics Pharmaceuticals, Inc. Process for preparing microparticles having a low residual solvent volume

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2946769A (en) * 1954-04-23 1960-07-26 Union Carbide Corp Linear polymers containing regularly recurring ester and amide linkages
US3025323A (en) * 1957-01-18 1962-03-13 Union Carbide Corp Amide diols and their esters
US4209607A (en) * 1978-05-12 1980-06-24 Ethicon, Inc. Polyesteramides derived from bis-oxamidodiols and dicarboxylic acids
US4226243A (en) * 1979-07-27 1980-10-07 Ethicon, Inc. Surgical devices of polyesteramides derived from bis-oxamidodiols and dicarboxylic acids
US4343931A (en) * 1979-12-17 1982-08-10 Minnesota Mining And Manufacturing Company Synthetic absorbable surgical devices of poly(esteramides)
US4429080A (en) * 1982-07-01 1984-01-31 American Cyanamid Company Synthetic copolymer surgical articles and method of manufacturing the same
US4529792A (en) * 1979-12-17 1985-07-16 Minnesota Mining And Manufacturing Company Process for preparing synthetic absorbable poly(esteramides)
US5522841A (en) * 1993-05-27 1996-06-04 United States Surgical Corporation Absorbable block copolymers and surgical articles fabricated therefrom

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3037269A1 (en) * 1980-10-02 1982-06-16 Beck & Co Ag Dr Thermosetting, amide and imide groups containing polycondensates
JP2575918B2 (en) * 1990-03-20 1997-01-29 ポリプラスチックス株式会社 Halogen-containing aromatic polyester amides and their preparation
US6120788A (en) * 1997-10-16 2000-09-19 Bioamide, Inc. Bioabsorbable triglycolic acid poly(ester-amide)s

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2946769A (en) * 1954-04-23 1960-07-26 Union Carbide Corp Linear polymers containing regularly recurring ester and amide linkages
US3025323A (en) * 1957-01-18 1962-03-13 Union Carbide Corp Amide diols and their esters
US4209607A (en) * 1978-05-12 1980-06-24 Ethicon, Inc. Polyesteramides derived from bis-oxamidodiols and dicarboxylic acids
US4226243A (en) * 1979-07-27 1980-10-07 Ethicon, Inc. Surgical devices of polyesteramides derived from bis-oxamidodiols and dicarboxylic acids
US4343931A (en) * 1979-12-17 1982-08-10 Minnesota Mining And Manufacturing Company Synthetic absorbable surgical devices of poly(esteramides)
US4529792A (en) * 1979-12-17 1985-07-16 Minnesota Mining And Manufacturing Company Process for preparing synthetic absorbable poly(esteramides)
US4429080A (en) * 1982-07-01 1984-01-31 American Cyanamid Company Synthetic copolymer surgical articles and method of manufacturing the same
US5522841A (en) * 1993-05-27 1996-06-04 United States Surgical Corporation Absorbable block copolymers and surgical articles fabricated therefrom

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Katayama, et al. "Synthesis of Alternating Polyamide Esters by Melt and Solution Polycondensations of N,N'-Di(6-hydroxycaproyl) dimines and N-6-Hydroxycaproyl Aminoalcohol with Terephthalic and Adipic Dimethyl Esters and Dichlorides" J. of Applied Polymer Science; 20: 975-994.
Katayama, et al. Synthesis of Alternating Polyamide Esters by Melt and Solution Polycondensations of N,N Di(6 hydroxycaproyl) dimines and N 6 Hydroxycaproyl Aminoalcohol with Terephthalic and Adipic Dimethyl Esters and Dichlorides J. of Applied Polymer Science ; 20: 975 994. *

Cited By (122)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6365172B1 (en) * 1997-10-16 2002-04-02 Bioamide, Inc. Device of bioabsorbable triglycolic acid poly(ester-amide)s, and methods of making the same
US20050191748A1 (en) * 1999-02-08 2005-09-01 Aderans Research Institute, Inc. Filamentary means for introducing agents into tissue of a living host
US7807211B2 (en) 1999-09-03 2010-10-05 Advanced Cardiovascular Systems, Inc. Thermal treatment of an implantable medical device
US20040054410A1 (en) * 2000-08-08 2004-03-18 Barrows Thomas H Scaffolds for tissue engineered hair
US7198641B2 (en) 2000-08-08 2007-04-03 Aderans Research Institute, Inc. Scaffolds for tissue engineered hair
US7691401B2 (en) 2000-09-28 2010-04-06 Advanced Cardiovascular Systems, Inc. Poly(butylmethacrylate) and rapamycin coated stent
US7807210B1 (en) 2000-10-31 2010-10-05 Advanced Cardiovascular Systems, Inc. Hemocompatible polymers on hydrophobic porous polymers
US20050100609A1 (en) * 2001-03-30 2005-05-12 Claude Charles D. Phase-separated polymer coatings
US8741378B1 (en) 2001-06-27 2014-06-03 Advanced Cardiovascular Systems, Inc. Methods of coating an implantable device
US7985440B2 (en) 2001-06-27 2011-07-26 Advanced Cardiovascular Systems, Inc. Method of using a mandrel to coat a stent
US10064982B2 (en) 2001-06-27 2018-09-04 Abbott Cardiovascular Systems Inc. PDLLA stent coating
US7682669B1 (en) 2001-07-30 2010-03-23 Advanced Cardiovascular Systems, Inc. Methods for covalently immobilizing anti-thrombogenic material into a coating on a medical device
US8303651B1 (en) 2001-09-07 2012-11-06 Advanced Cardiovascular Systems, Inc. Polymeric coating for reducing the rate of release of a therapeutic substance from a stent
US20040068284A1 (en) * 2002-01-29 2004-04-08 Barrows Thomas H. Method for stimulating hair growth and kit for carrying out said method
US8961588B2 (en) 2002-03-27 2015-02-24 Advanced Cardiovascular Systems, Inc. Method of coating a stent with a release polymer for 40-O-(2-hydroxy)ethyl-rapamycin
US8173199B2 (en) 2002-03-27 2012-05-08 Advanced Cardiovascular Systems, Inc. 40-O-(2-hydroxy)ethyl-rapamycin coated stent
US8506617B1 (en) 2002-06-21 2013-08-13 Advanced Cardiovascular Systems, Inc. Micronized peptide coated stent
US7875286B2 (en) 2002-06-21 2011-01-25 Advanced Cardiovascular Systems, Inc. Polycationic peptide coatings and methods of coating implantable medical devices
US7901703B2 (en) 2002-06-21 2011-03-08 Advanced Cardiovascular Systems, Inc. Polycationic peptides for cardiovascular therapy
US7803394B2 (en) 2002-06-21 2010-09-28 Advanced Cardiovascular Systems, Inc. Polycationic peptide hydrogel coatings for cardiovascular therapy
US7794743B2 (en) 2002-06-21 2010-09-14 Advanced Cardiovascular Systems, Inc. Polycationic peptide coatings and methods of making the same
US9084671B2 (en) 2002-06-21 2015-07-21 Advanced Cardiovascular Systems, Inc. Methods of forming a micronized peptide coated stent
US8067023B2 (en) 2002-06-21 2011-11-29 Advanced Cardiovascular Systems, Inc. Implantable medical devices incorporating plasma polymerized film layers and charged amino acids
US7803406B2 (en) 2002-06-21 2010-09-28 Advanced Cardiovascular Systems, Inc. Polycationic peptide coatings and methods of coating implantable medical devices
US8986726B2 (en) 2002-12-11 2015-03-24 Abbott Cardiovascular Systems Inc. Biocompatible polyacrylate compositions for medical applications
US8871236B2 (en) 2002-12-11 2014-10-28 Abbott Cardiovascular Systems Inc. Biocompatible polyacrylate compositions for medical applications
US7776926B1 (en) 2002-12-11 2010-08-17 Advanced Cardiovascular Systems, Inc. Biocompatible coating for implantable medical devices
US8871883B2 (en) 2002-12-11 2014-10-28 Abbott Cardiovascular Systems Inc. Biocompatible coating for implantable medical devices
US7758880B2 (en) 2002-12-11 2010-07-20 Advanced Cardiovascular Systems, Inc. Biocompatible polyacrylate compositions for medical applications
US8647655B2 (en) 2002-12-11 2014-02-11 Abbott Cardiovascular Systems Inc. Biocompatible polyacrylate compositions for medical applications
US7648725B2 (en) 2002-12-12 2010-01-19 Advanced Cardiovascular Systems, Inc. Clamp mandrel fixture and a method of using the same to minimize coating defects
US8435550B2 (en) 2002-12-16 2013-05-07 Abbot Cardiovascular Systems Inc. Anti-proliferative and anti-inflammatory agent combination for treatment of vascular disorders with an implantable medical device
US8586069B2 (en) 2002-12-16 2013-11-19 Abbott Cardiovascular Systems Inc. Anti-proliferative and anti-inflammatory agent combination for treatment of vascular disorders
US9175162B2 (en) 2003-05-08 2015-11-03 Advanced Cardiovascular Systems, Inc. Methods for forming stent coatings comprising hydrophilic additives
US8673334B2 (en) 2003-05-08 2014-03-18 Abbott Cardiovascular Systems Inc. Stent coatings comprising hydrophilic additives
US7785512B1 (en) 2003-07-31 2010-08-31 Advanced Cardiovascular Systems, Inc. Method and system of controlled temperature mixing and molding of polymers with active agents for implantable medical devices
US8197879B2 (en) 2003-09-30 2012-06-12 Advanced Cardiovascular Systems, Inc. Method for selectively coating surfaces of a stent
US9114198B2 (en) 2003-11-19 2015-08-25 Advanced Cardiovascular Systems, Inc. Biologically beneficial coatings for implantable devices containing fluorinated polymers and methods for fabricating the same
US8192752B2 (en) 2003-11-21 2012-06-05 Advanced Cardiovascular Systems, Inc. Coatings for implantable devices including biologically erodable polyesters and methods for fabricating the same
USRE45744E1 (en) 2003-12-01 2015-10-13 Abbott Cardiovascular Systems Inc. Temperature controlled crimping
US8052912B2 (en) 2003-12-01 2011-11-08 Advanced Cardiovascular Systems, Inc. Temperature controlled crimping
US7786249B2 (en) 2003-12-19 2010-08-31 Advanced Cardiovascular Systems, Inc. Biobeneficial polyamide/polyethylene glycol polymers for use with drug eluting stents
US7772359B2 (en) 2003-12-19 2010-08-10 Advanced Cardiovascular Systems, Inc. Biobeneficial polyamide/polyethylene glycol polymers for use with drug eluting stents
US8685431B2 (en) 2004-03-16 2014-04-01 Advanced Cardiovascular Systems, Inc. Biologically absorbable coatings for implantable devices based on copolymers having ester bonds and methods for fabricating the same
US20050214344A1 (en) * 2004-03-26 2005-09-29 Aderans Research Institute, Inc. Tissue engineered biomimetic hair follicle graft
US7597885B2 (en) 2004-03-26 2009-10-06 Aderans Research Institute, Inc. Tissue engineered biomimetic hair follicle graft
US8778014B1 (en) 2004-03-31 2014-07-15 Advanced Cardiovascular Systems, Inc. Coatings for preventing balloon damage to polymer coated stents
US8293890B2 (en) 2004-04-30 2012-10-23 Advanced Cardiovascular Systems, Inc. Hyaluronic acid based copolymers
US9101697B2 (en) 2004-04-30 2015-08-11 Abbott Cardiovascular Systems Inc. Hyaluronic acid based copolymers
US7820732B2 (en) 2004-04-30 2010-10-26 Advanced Cardiovascular Systems, Inc. Methods for modulating thermal and mechanical properties of coatings on implantable devices
US9561309B2 (en) 2004-05-27 2017-02-07 Advanced Cardiovascular Systems, Inc. Antifouling heparin coatings
US9375445B2 (en) 2004-06-18 2016-06-28 Abbott Cardiovascular Systems Inc. Heparin prodrugs and drug delivery stents formed therefrom
US9364498B2 (en) 2004-06-18 2016-06-14 Abbott Cardiovascular Systems Inc. Heparin prodrugs and drug delivery stents formed therefrom
US8017140B2 (en) 2004-06-29 2011-09-13 Advanced Cardiovascular System, Inc. Drug-delivery stent formulations for restenosis and vulnerable plaque
US7758881B2 (en) 2004-06-30 2010-07-20 Advanced Cardiovascular Systems, Inc. Anti-proliferative and anti-inflammatory agent combination for treatment of vascular disorders with an implantable medical device
US8586075B2 (en) 2004-07-30 2013-11-19 Abbott Cardiovascular Systems Inc. Coatings for implantable devices comprising poly(hydroxy-alkanoates) and diacid linkages
US9580558B2 (en) 2004-07-30 2017-02-28 Abbott Cardiovascular Systems Inc. Polymers containing siloxane monomers
US8758801B2 (en) 2004-07-30 2014-06-24 Abbott Cardiocascular Systems Inc. Coatings for implantable devices comprising poly(hydroxy-alkanoates) and diacid linkages
US8357391B2 (en) 2004-07-30 2013-01-22 Advanced Cardiovascular Systems, Inc. Coatings for implantable devices comprising poly (hydroxy-alkanoates) and diacid linkages
US20060062770A1 (en) * 2004-08-13 2006-03-23 Aderans Research Institute, Inc. Organogenesis from dissociated cells
US7648727B2 (en) 2004-08-26 2010-01-19 Advanced Cardiovascular Systems, Inc. Methods for manufacturing a coated stent-balloon assembly
US7766884B2 (en) 2004-08-31 2010-08-03 Advanced Cardiovascular Systems, Inc. Polymers of fluorinated monomers and hydrophilic monomers
US8110211B2 (en) 2004-09-22 2012-02-07 Advanced Cardiovascular Systems, Inc. Medicated coatings for implantable medical devices including polyacrylates
US8603634B2 (en) 2004-10-27 2013-12-10 Abbott Cardiovascular Systems Inc. End-capped poly(ester amide) copolymers
US9067000B2 (en) 2004-10-27 2015-06-30 Abbott Cardiovascular Systems Inc. End-capped poly(ester amide) copolymers
US7749263B2 (en) 2004-10-29 2010-07-06 Abbott Cardiovascular Systems Inc. Poly(ester amide) filler blends for modulation of coating properties
US8609123B2 (en) 2004-11-29 2013-12-17 Advanced Cardiovascular Systems, Inc. Derivatized poly(ester amide) as a biobeneficial coating
US7892592B1 (en) 2004-11-30 2011-02-22 Advanced Cardiovascular Systems, Inc. Coating abluminal surfaces of stents and other implantable medical devices
US9339592B2 (en) 2004-12-22 2016-05-17 Abbott Cardiovascular Systems Inc. Polymers of fluorinated monomers and hydrocarbon monomers
US7699889B2 (en) 2004-12-27 2010-04-20 Advanced Cardiovascular Systems, Inc. Poly(ester amide) block copolymers
US8007775B2 (en) 2004-12-30 2011-08-30 Advanced Cardiovascular Systems, Inc. Polymers containing poly(hydroxyalkanoates) and agents for use with medical articles and methods of fabricating the same
US7795467B1 (en) 2005-04-26 2010-09-14 Advanced Cardiovascular Systems, Inc. Bioabsorbable, biobeneficial polyurethanes for use in medical devices
US8778375B2 (en) 2005-04-29 2014-07-15 Advanced Cardiovascular Systems, Inc. Amorphous poly(D,L-lactide) coating
US7823533B2 (en) 2005-06-30 2010-11-02 Advanced Cardiovascular Systems, Inc. Stent fixture and method for reducing coating defects
US8021676B2 (en) 2005-07-08 2011-09-20 Advanced Cardiovascular Systems, Inc. Functionalized chemically inert polymers for coatings
US7785647B2 (en) 2005-07-25 2010-08-31 Advanced Cardiovascular Systems, Inc. Methods of providing antioxidants to a drug containing product
US7735449B1 (en) 2005-07-28 2010-06-15 Advanced Cardiovascular Systems, Inc. Stent fixture having rounded support structures and method for use thereof
US20070148138A1 (en) * 2005-11-22 2007-06-28 Aderans Research Institute, Inc. Hair follicle graft from tissue engineered skin
US20100178683A1 (en) * 2005-11-22 2010-07-15 Aderans Research Insitute, Inc. Hair follicle graft from tissue engineered skin
US20070122387A1 (en) * 2005-11-22 2007-05-31 Aderans Research Institute, Inc. Hair grafts derived from plucked hair
US9023380B2 (en) 2005-11-22 2015-05-05 Aderans Research Institute, Inc. Hair follicle graft from tissue engineered skin
US8007526B2 (en) 2005-12-01 2011-08-30 Bezwada Biomedical, Llc Difunctionalized aromatic compounds and polymers therefrom
US7976891B1 (en) 2005-12-16 2011-07-12 Advanced Cardiovascular Systems, Inc. Abluminal stent coating apparatus and method of using focused acoustic energy
US7867547B2 (en) 2005-12-19 2011-01-11 Advanced Cardiovascular Systems, Inc. Selectively coating luminal surfaces of stents
US8067025B2 (en) 2006-02-17 2011-11-29 Advanced Cardiovascular Systems, Inc. Nitric oxide generating medical devices
US7713637B2 (en) 2006-03-03 2010-05-11 Advanced Cardiovascular Systems, Inc. Coating containing PEGylated hyaluronic acid and a PEGylated non-hyaluronic acid polymer
US7985441B1 (en) 2006-05-04 2011-07-26 Yiwen Tang Purification of polymers for coating applications
US8003156B2 (en) 2006-05-04 2011-08-23 Advanced Cardiovascular Systems, Inc. Rotatable support elements for stents
US8637110B2 (en) 2006-05-04 2014-01-28 Advanced Cardiovascular Systems, Inc. Rotatable support elements for stents
US8304012B2 (en) 2006-05-04 2012-11-06 Advanced Cardiovascular Systems, Inc. Method for drying a stent
US8465789B2 (en) 2006-05-04 2013-06-18 Advanced Cardiovascular Systems, Inc. Rotatable support elements for stents
US8741379B2 (en) 2006-05-04 2014-06-03 Advanced Cardiovascular Systems, Inc. Rotatable support elements for stents
US8596215B2 (en) 2006-05-04 2013-12-03 Advanced Cardiovascular Systems, Inc. Rotatable support elements for stents
US8069814B2 (en) 2006-05-04 2011-12-06 Advanced Cardiovascular Systems, Inc. Stent support devices
US7775178B2 (en) 2006-05-26 2010-08-17 Advanced Cardiovascular Systems, Inc. Stent coating apparatus and method
US9561351B2 (en) 2006-05-31 2017-02-07 Advanced Cardiovascular Systems, Inc. Drug delivery spiral coil construct
US8568764B2 (en) 2006-05-31 2013-10-29 Advanced Cardiovascular Systems, Inc. Methods of forming coating layers for medical devices utilizing flash vaporization
US8703167B2 (en) 2006-06-05 2014-04-22 Advanced Cardiovascular Systems, Inc. Coatings for implantable medical devices for controlled release of a hydrophilic drug and a hydrophobic drug
US8029816B2 (en) 2006-06-09 2011-10-04 Abbott Cardiovascular Systems Inc. Medical device coated with a coating containing elastin pentapeptide VGVPG
US8778376B2 (en) 2006-06-09 2014-07-15 Advanced Cardiovascular Systems, Inc. Copolymer comprising elastin pentapeptide block and hydrophilic block, and medical device and method of treating
US8114150B2 (en) 2006-06-14 2012-02-14 Advanced Cardiovascular Systems, Inc. RGD peptide attached to bioabsorbable stents
US8118863B2 (en) 2006-06-14 2012-02-21 Abbott Cardiovascular Systems Inc. RGD peptide attached to bioabsorbable stents
US8808342B2 (en) 2006-06-14 2014-08-19 Abbott Cardiovascular Systems Inc. Nanoshell therapy
US8062350B2 (en) 2006-06-14 2011-11-22 Abbott Cardiovascular Systems Inc. RGD peptide attached to bioabsorbable stents
US8603530B2 (en) 2006-06-14 2013-12-10 Abbott Cardiovascular Systems Inc. Nanoshell therapy
US8048448B2 (en) 2006-06-15 2011-11-01 Abbott Cardiovascular Systems Inc. Nanoshells for drug delivery
US8592036B2 (en) 2006-06-23 2013-11-26 Abbott Cardiovascular Systems Inc. Nanoshells on polymers
US8017237B2 (en) 2006-06-23 2011-09-13 Abbott Cardiovascular Systems, Inc. Nanoshells on polymers
US8293367B2 (en) 2006-06-23 2012-10-23 Advanced Cardiovascular Systems, Inc. Nanoshells on polymers
US9028859B2 (en) 2006-07-07 2015-05-12 Advanced Cardiovascular Systems, Inc. Phase-separated block copolymer coatings for implantable medical devices
US8703169B1 (en) 2006-08-15 2014-04-22 Abbott Cardiovascular Systems Inc. Implantable device having a coating comprising carrageenan and a biostable polymer
US8597673B2 (en) 2006-12-13 2013-12-03 Advanced Cardiovascular Systems, Inc. Coating of fast absorption or dissolution
US20080161489A1 (en) * 2006-12-28 2008-07-03 Adel Farhan Halasa Rubbery block polymers containing polylactone and rubber compounds including the same
US7662883B2 (en) 2006-12-28 2010-02-16 The Goodyear Tire & Rubber Company Rubbery block polymers containing polylactone and rubber compounds including the same
US8147769B1 (en) 2007-05-16 2012-04-03 Abbott Cardiovascular Systems Inc. Stent and delivery system with reduced chemical degradation
US9056155B1 (en) 2007-05-29 2015-06-16 Abbott Cardiovascular Systems Inc. Coatings having an elastic primer layer
US7985537B2 (en) 2007-06-12 2011-07-26 Aderans Research Institute, Inc. Methods for determining the hair follicle inductive properties of a composition
US20080311044A1 (en) * 2007-06-12 2008-12-18 Aderans Research Institute, Inc. Methods of determining hair follicle inductive properties
US8109904B1 (en) 2007-06-25 2012-02-07 Abbott Cardiovascular Systems Inc. Drug delivery medical devices
US8048441B2 (en) 2007-06-25 2011-11-01 Abbott Cardiovascular Systems, Inc. Nanobead releasing medical devices
US8309132B2 (en) 2008-05-16 2012-11-13 Bezwada Biomedical, Llc Bioabsorbable polyesteramides and uses thereof
US10076591B2 (en) 2010-03-31 2018-09-18 Abbott Cardiovascular Systems Inc. Absorbable coating for implantable device

Also Published As

Publication number Publication date
US6365172B1 (en) 2002-04-02

Similar Documents

Publication Publication Date Title
US10136982B2 (en) Polyhydroxyalkanoate medical textiles and fibers
CA2304992C (en) Self-cohering, continuous filament non-woven webs
US5578662A (en) Bioabsorbable branched polymers containing units derived from dioxanone and medical/surgical devices manufactured therefrom
US6420027B2 (en) Biodegradable complex fiber and method for producing the same
EP2066725B1 (en) Polyester compositions, methods of manufacturing said compositions, and articles made therefrom
Cohn et al. Biodegradable PEO/PLA block copolymers
JP4795595B2 (en) Adaptation of the crystalline copolymer derived from amorphous polymeric polyaxial initiator and the initiator
US6113624A (en) Absorbable elastomeric polymer
AU741145B2 (en) Biodegradable terephthalate polyester-poly(phosphate) polymers, compositions, articles, and methods for making and using the same
EP0794211B1 (en) Blends containing absorbable polyoxaamides
US5531998A (en) Polycarbonate-based block copolymers and devices
CA1255844A (en) Radiation sterilizable absorbable polymeric materials and methods for manufacturing the same
EP1591132B1 (en) Poly(lactide-co-glycolide) terpolymers and medical devices containing same
US5349045A (en) Polymer derived from cyclic amide and medical devices manufactured therefrom
KR100253712B1 (en) Bioabsorbable polymer and process for preparing the same
US5951997A (en) Aliphatic polyesters of ε-caprolactone, p-dioxanone and gycolide
AU729552B2 (en) Monomers derived from hydroxy acids and polymers prepared therefrom
US4605730A (en) Surgical articles of copolymers of glycolide and ε-caprolactone and methods of producing the same
US5914387A (en) Polyesteramides with amino acid-derived groups alternating with alpha-hydroxyacid-derived groups and surgical articles made therefrom
JP2603229B2 (en) The method of manufacturing a crystalline copolymer of p- dioxanone and lactide
JP3126637B2 (en) Biocompatible block copolymer
FI73447C (en) Kirurgisk sutur foerfarandet Foer och dess framstaellning.
US5912225A (en) Biodegradable poly (phosphoester-co-desaminotyrosyl L-tyrosine ester) compounds, compositions, articles and methods for making and using the same
US4857602A (en) Bioabsorbable surgical suture coating
JP4326839B2 (en) Mounting method for the absorbent tissue scaffold relative to the stationary device

Legal Events

Date Code Title Description
AS Assignment

Owner name: BIOAMIDE, INC., MINNESOTA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:BARROWS, THOMAS H.;REEL/FRAME:009788/0517

Effective date: 19990204

AS Assignment

Owner name: ADERANS RESEARCH INSTITUTE, INC., CALIFORNIA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:BIOAMIDE, INC.;REEL/FRAME:014083/0145

Effective date: 20020628

FPAY Fee payment

Year of fee payment: 4

REMI Maintenance fee reminder mailed
LAPS Lapse for failure to pay maintenance fees
FP Expired due to failure to pay maintenance fee

Effective date: 20080919